Evidence map›Paper›PMID 33221554›Full record

ArticleMolecular metabolism2021

Behavioural and neurochemical mechanisms underpinning the feeding-suppressive effect of GLP-1/CCK combinatorial therapy.

Emma Roth, Simon Benoit, Baptiste Quentin, Brian Lam, Sarah Will, Marcella Ma, Nick Heeley, Tamana Darwish, Yashaswi Shrestha, Fiona Gribble and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.3field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 2 institutions in 1 country.

Emma RothMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 OQQ, UK.
Simon BenoitMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 OQQ, UK.
Baptiste QuentinMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 OQQ, UK.
Brian LamMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 OQQ, UK.
Sarah WillCardiovascular, Renal, and Metabolic Diseases, MedImmune LLC, Gaithersburg, MD 20878, USA.
Marcella MaMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 OQQ, UK.
Nick HeeleyMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 OQQ, UK.
Tamana DarwishMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 OQQ, UK.
Yashaswi ShresthaEarly Oncology, Translational Medicine, MedImmune LLC, Gaithersburg, MD 20878, USA.
Fiona GribbleMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 OQQ, UK.
Frank ReimannMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 OQQ, UK.
Irina PshenichnayaWellcome-MRC Cambridge Stem Cell Institute, Cambridge, UK.
Giles YeoMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 OQQ, UK.
David J BakerCardiovascular, Renal and Metabolic Diseases, MedImmune Ltd., Cambridge, UK.
James L TrevaskisCardiovascular, Renal and Metabolic Diseases, MedImmune Ltd., Cambridge, UK.
Clemence BlouetMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 OQQ, UK. Electronic address: csb69@medschl.cam.ac.uk.
University of Cambridge · GBWellcome/MRC Cambridge Stem Cell Institute · GB

Funding

Medical Research Council MC_UU_00014/3Medical Research Council MC_UU_00014/5Medical Research Council MC_UU_00014/6Medical Research Council MC_UU_12012/3Medical Research Council MC_UU_12012/5Medical Research Council MR/M501736/1Wellcome TrustWellcome Trust 100574/Z/12/Z
6 · The paper itself

Abstract

objectivesCombinatorial therapies are under intense investigation to develop more efficient anti-obesity drugs; however, little is known about how they act in the brain to produce enhanced anorexia and weight loss. The goal of this study was to identify the brain sites and neuronal populations engaged during the co-administration of GLP-1R and CCK1R agonists, an efficient combination therapy in obese rodents.

methodsWe measured acute and long-term feeding and body weight responses and neuronal activation patterns throughout the neuraxis and in specific neuronal subsets in response to GLP-1R and CCK1R agonists administered alone or in combination in lean and high-fat diet fed mice. We used PhosphoTRAP to obtain unbiased molecular markers for neuronal populations selectively activated by the combination of the two agonists.

resultsThe initial anorectic response to GLP-1R and CCK1R co-agonism was mediated by a reduction in meal size, but over a few hours, a reduction in meal number accounted for the sustained feeding suppressive effects. The nucleus of the solitary tract (NTS) is one of the few brain sites where GLP-1R and CCK1R signalling interact to produce enhanced neuronal activation. None of the previously categorised NTS neuronal subpopulations relevant to feeding behaviour were implicated in this increased activation. However, we identified NTS/AP Calcrl

conclusionsCollectively, these studies indicated that circuit-level integration of GLP-1R and CCK1R co-agonism in discrete brain nuclei including the NTS produces enhanced rapid and sustained appetite suppression and weight loss.

Indexed as

AnimalsAnti-Obesity AgentsAppetite RegulationBrainDiet, High-FatEatingFeeding BehaviorGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorMaleMiceMice, Inbred C57BLNeuronsObesityReceptors, CholecystokininSolitary NucleusAnti-Obesity AgentsGlp1r protein, mouseGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorReceptors, CholecystokininCCKCombinatorial therapyGLP-1HungerNucleus of the solitary tractObesitySatiety

Identifiers

PMID33221554
PMCPMC7720077
OpenAlexW3109723678

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.